A novel germline mutation of PTEN associated with brain tumours of multiple lineages

Br J Cancer. 2002 May 20;86(10):1586-91. doi: 10.1038/sj.bjc.6600206.


We have identified a novel germline mutation in the PTEN tumour suppressor gene. The mutation was identified in a patient with a glioma, and turned out to be a heterozygous germline mutation of PTEN (Arg234Gln), without loss of heterozygosity in tumour DNA. The biological consequences of this germline mutation were investigated by means of transfection studies of the mutant PTEN molecule compared to wild-type PTEN. In contrast to the wild-type molecule, the mutant PTEN protein is not capable of inducing apoptosis, induces increased cell proliferation and leads to high constitutive PKB/Akt activation, which cannot be increased anymore by stimulation with insulin. The reported patient, in addition to glioma, had suffered from benign meningioma in the past but did not show any clinical signs of Cowden disease or other hereditary diseases typically associated with PTEN germline mutations. The functional consequences of the mutation in transfection studies are consistent with high proliferative activity. Together, these findings suggest that the Arg234Gln missense mutation in PTEN has oncogenic properties and predisposes to brain tumours of multiple lineages.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Substitution*
  • Apoptosis / genetics
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cell Division
  • Cell Lineage
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Enzyme Activation / drug effects
  • Frontal Lobe* / pathology
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • Humans
  • Insulin / pharmacology
  • Loss of Heterozygosity
  • Male
  • Meningeal Neoplasms / genetics*
  • Meningeal Neoplasms / pathology
  • Meningioma / genetics*
  • Meningioma / pathology
  • Models, Molecular
  • Mutation, Missense*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology
  • Oligodendroglioma / genetics*
  • Oligodendroglioma / pathology
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / chemistry
  • Phosphoric Monoester Hydrolases / genetics*
  • Phosphoric Monoester Hydrolases / physiology
  • Point Mutation*
  • Protein Conformation
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Transfection
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / physiology
  • U937 Cells / drug effects
  • U937 Cells / enzymology


  • DNA, Neoplasm
  • Insulin
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • AKT1 protein, human
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human